The use of hydroxypropylmethyl cellulose as a rate controlling hydrophilic polymer in controlled release formulations is well-documented.
A major problem associated with most existing controlled release systems containing hydroxypropylmethyl cellulose and other pH independent rate controlling polymers is that they provide no control over drug release into media of differing pH, where drug solubility is dependent upon pH.
A sustained or controlled release product providing pH-independent drug release is essential to avoid problems of bioavailability variation during therapy if fluctuations in gastrointestinal pH can occur. There is, of course, the natural pH gradient down the gut from the acidity of the stomach, through the weakly acidic duodenum to the neutral environment of the small intestine. Superimposed on this are possible fluctuations in pH arising from dietary changes. For example, feeding or fasting have effects on stomach acidity and this would affect a product with pH-dependent drug release if it were taken with or between meals. Other pH changes can be drug induced. For example, the treatment of duodenal or gastric ulcer with H.sub.2 -receptor antagonists like cimetidine or ranitidine may markedly raise basal gastric pH.
Consistent sustained release drug product performance against all these challenges would be highly desirable.
Alginate based systems have been proposed as oral sustained release matrix dose forms. Gel formation in these systems is governed by an interaction between calcium ions and alginic acid. "Gel Formation iith Alginate", Data Sheet D1571, Alginate Industries Limited, London, discloses that "gel formation is obtained by steady and uniform release of calcium, or other cations capable of forming an insoluble alginate, into the alginate solution". Other workers (Stockwell, A. F. et al., Journal Controlled Release, 3 (1986) 167-175) have employed the calcium gelled alginate system in combination with CO.sub.2 generating excipients to yield a tablet that floats on the gastric contents. Such systems are not intended to pass down the GI tract and release drug in variable pH environments.